Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

That is very true, but some of the factors that lead to antibiotic resistance, namely incomplete/inconsistent use of the chemical agent, isn't going to be a factor. At least not in my mind, but my highest level of immunology education was in dental school and I sit around cutting teeth and prescribing amoxicillin all day, so what do I know. I'm at least a minor part of the problem.

I wonder how the deaths of all the other bacteria affect the surrounding bath? Maybe some chemical gets released when the membranes for the other bacteria are pierced that is sensed by the remaining bacteria or it affects the pH or something.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

It's extremely depressing how often these types of articles are making the rounds nowadays. It's getting to be every couple weeks it seems like there's a new report of how we're dooming ourselves to one day be wiped out by super bacteria.

It’s unclear what genes the system is controlling, but evidence so far suggests that genetic tinkering allows the cell to make its outer membrane less negatively charged to thwart colistin. The antibiotic is positively charged and seems to kill by breaking down bacterial cell's otherwise negatively charged outer membranes.

I wonder how the deaths of all the other bacteria affect the surrounding bath? Maybe some chemical gets released when the membranes for the other bacteria are pierced that is sensed by the remaining bacteria or it affects the pH or something.

Edit: grammar

The article mentioned that when the bacteria was grown in a colisitin environment the resistant strains dominated and still did well. In that situation there are very few dead bacteria feeding the bath. And once the colistin is removed the non-resistant strains once again become dominant.

It's extremely depressing how often these types of articles are making the rounds nowadays. It's getting to be every couple weeks it seems like there's a new report of how we're dooming ourselves to one day be wiped out by super bacteria.

Fortunately, a century after we're all wiped out and the antibiotic pressure is relieved, the bacteria will probably mostly revert to wild-type because it's more efficient in the absence of antibiotics.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

That is very true, but some of the factors that lead to antibiotic resistance, namely incomplete/inconsistent use of the chemical agent, isn't going to be a factor. At least not in my mind, but my highest level of immunology education was in dental school and I sit around cutting teeth and prescribing amoxicillin all day, so what do I know. I'm at least a minor part of the problem.

That's a good point, misuse of vaccines is a lot harder than misuse of antibiotics. I come from a microbiology background and if I've learned anything its that damn, they are adaptable little monsters.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

Unfortunately, bacteriophages are the fusion of the medical world. Always very promising and always a couple of decades away. I know there have been successes but they really remain well outside of mainstream thinking.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

Unfortunately, bacteriophages are the fusion of the medical world. Always very promising and always a couple of decades away. I know there have been successes but they really remain well outside of mainstream thinking.

You ain't just a'kidding. I can remember reading an Upton Sinclair novel in high school that invoked bacteriophages as a magic bullet against bacteria...and high school was a very long time ago.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

Unfortunately, bacteriophages are the fusion of the medical world. Always very promising and always a couple of decades away. I know there have been successes but they really remain well outside of mainstream thinking.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

That is very true, but some of the factors that lead to antibiotic resistance, namely incomplete/inconsistent use of the chemical agent, isn't going to be a factor. At least not in my mind, but my highest level of immunology education was in dental school and I sit around cutting teeth and prescribing amoxicillin all day, so what do I know. I'm at least a minor part of the problem.

That's a good point, misuse of vaccines is a lot harder than misuse of antibiotics. I come from a microbiology background and if I've learned anything its that damn, they are adaptable little monsters.

Unfortunately, many bacteria have some pretty neat ways of avoiding antibody defenses. Structurally many have thick coats that prevent binding of antibodies to core parts of the bacterium, they can also alter their environment (this is simplification) to create an environment non-conducive to antibody mediated destruction.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

Unfortunately, bacteriophages are the fusion of the medical world. Always very promising and always a couple of decades away. I know there have been successes but they really remain well outside of mainstream thinking.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

Yeah, but that assumes that technology was the stumbling block in the first place. If there are other problems like triggering adverse reactions of their own, improved DNA technology isn't going to help much. I'm not trying to knock them, I'm just trying to be realistic about their chance for success.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

Unfortunately, bacteriophages are the fusion of the medical world. Always very promising and always a couple of decades away. I know there have been successes but they really remain well outside of mainstream thinking.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

Which is going to be great in many parts of the world... but not in the US.Here they are going to need to spend a couple billion dollars and at least a decade to study every little change before they could treat the patient, even if the patient only has a week to live without it.

While there is some need for safety (as if the people making these cures have no concern or actively want their treatment to be harmful), putting all the incentives on letting people die from treatable conditions to avoid any patients having unforeseen side-effects is a net harm to society.

The lack of new antibiotics is the brazen shame of pharma. Why spend $ on desperately needed new medicines when we can patent a new daily pill for restless finger syndrome...?

And the answer is that for routine infections, it's a solved problem taken care of by generics. And for the super-resistant infections, you just spent a big chunk of a billion dollars developing a drug that the FDA will only allow to be used as a last resort. And even when it's finally used successfully, it's only going to be dosed for a couple of weeks. So you've effectively flushed a big chunk of a billion dollars down the toilet, and the shareholders will flush management after it.

This is a classic case where government should be either developing, outsourcing, or otherwise putting funds into developing drugs for a serious (potentially existential!) health problem that is not a fit for the big pharma business model. Of course, since we only believe in destroying government these days, that isn't going to happen soon.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

Which is going to be great in many parts of the world... but not in the US.Here they are going to need to spend a couple billion dollars and at least a decade to study every little change before they could treat the patient, even if the patient only has a week to live without it.

While there is some need for safety (as if the people making these cures have no concern or actively want their treatment to be harmful), putting all the incentives on letting people die from treatable conditions to avoid any patients having unforeseen side-effects is a net harm to society.

I get what you are saying. Part of me agrees. That said, the first rule of medicine, " First, do no harm. "

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

Bacteriophages are very promising. Anything easy to resist is dead, so we have millions of years of evolution working for us.

Unfortunately, bacteriophages are the fusion of the medical world. Always very promising and always a couple of decades away. I know there have been successes but they really remain well outside of mainstream thinking.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

Yeah, but that assumes that technology was the stumbling block in the first place. If there are other problems like triggering adverse reactions of their own, improved DNA technology isn't going to help much. I'm not trying to knock them, I'm just trying to be realistic about their chance for success.

Adverse reactions aren't the problem. Bacteriophages attack prokaryotes not eukaryotes. Historically the problem with phage therapy has been the need to wait for successive generations of phages to evolve in response to an in vitro culture of the resident infection and produce lethal results. In other words, it's just too fucking time-consuming. Aggressive bacterial infections move with astonishing speed. The Soviets had some limited success, but the speed and efficacy of antibiotics just couldn't be touched by phages.

That all changes when you can rapidly sequence the infection colony genome then employ direct editing of a stock phage and produce large quantities in perhaps a day; all this is very much a possibility with tech we have already. The only stumbling block is cutting costs. I have a friend that's done a fair amount of work in a research lab using these tools and the takeaway is that it just keeps getting cheaper by the day.

We are about to enter an era of bioscience that makes our historical efforts look like the drawings of a talented toddler compared to Vincent van Gogh. It's hard to overstate how massively influential the resolution and precision CRISPR/Cas9 is as compared to previous tech like zinc fingers.

Adverse reactions aren't the problem. Bacteriophages attack prokaryotes not eukaryotes. Historically the problem with phage therapy has been the need to wait for successive generations of phages to evolve in response to an in vitro culture of the resident infection and produce lethal results. In other words, it's just too fucking time-consuming. Aggressive bacterial infections move with astonishing speed. The Soviets had some limited success, but the speed and efficacy of antibiotics just couldn't be touched by phages.

That all changes when you can rapidly sequence the infection colony genome then employ direct editing of a stock phage and produce large quantities in perhaps a day; all this is very much a possibility with tech we have already. The only stumbling block is cutting costs. I have a friend that's done a fair amount of work in a research lab using these tools and the takeaway is that it just keeps getting cheaper by the day.

Adverse reactions ARE a potential issue. I know that bacteriophage aren't attacking eukaryotic cells, but they are a foreign substance in the body and that most definitely has the chance to trigger a reaction. It's a well-known problem for biotherapeutics.

Adverse reactions aren't the problem. Bacteriophages attack prokaryotes not eukaryotes. Historically the problem with phage therapy has been the need to wait for successive generations of phages to evolve in response to an in vitro culture of the resident infection and produce lethal results. In other words, it's just too fucking time-consuming. Aggressive bacterial infections move with astonishing speed. The Soviets had some limited success, but the speed and efficacy of antibiotics just couldn't be touched by phages.

That all changes when you can rapidly sequence the infection colony genome then employ direct editing of a stock phage and produce large quantities in perhaps a day; all this is very much a possibility with tech we have already. The only stumbling block is cutting costs. I have a friend that's done a fair amount of work in a research lab using these tools and the takeaway is that it just keeps getting cheaper by the day.

Adverse reactions ARE a potential issue. I know that bacteriophage aren't attacking eukaryotic cells, but they are a foreign substance in the body and that most definitely has the chance to trigger a reaction. It's a well-known problem for biotherapeutics.

Not to mention the possibility the bacteriophages attack the wrong bacteria or start making toxins.

I think phages may be viable in the near future with the rapid improvements in genetic sequencing and editing that have been made recently. We're fast approaching the point where a regional hospital could very well afford the equipment and expertise needed to effectively sequence an infection, develop a phage design, and then edit DNA to produce it and culture a population in a few days.

Which is going to be great in many parts of the world... but not in the US.Here they are going to need to spend a couple billion dollars and at least a decade to study every little change before they could treat the patient, even if the patient only has a week to live without it.

While there is some need for safety (as if the people making these cures have no concern or actively want their treatment to be harmful), putting all the incentives on letting people die from treatable conditions to avoid any patients having unforeseen side-effects is a net harm to society.

I get what you are saying. Part of me agrees. That said, the first rule of medicine, " First, do no harm. "

Well that was the traditional thing, but now there is a Faringi rider.

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

That is very true, but some of the factors that lead to antibiotic resistance, namely incomplete/inconsistent use of the chemical agent, isn't going to be a factor. At least not in my mind, but my highest level of immunology education was in dental school and I sit around cutting teeth and prescribing amoxicillin all day, so what do I know. I'm at least a minor part of the problem.

That's not clear at all. Vaccines *still* work in a dynamic system ('life finds a way ...') and there will be selective pressures for the little critters to escape whatever bullet you send them.

And we're finding that this 'incomplete / inconsistent' use theory is really a small issue. We have impressively little good info on how long to use a given antibiotic.

But the long, hard slog is correct. This is a war - and so far, the bugs are winning. They outnumber you a couple of billion to one even in your own body. Think of that - you're outnumbered even in yourself....

Perhaps it is time that we start looking a lot closer for some unique antigens on some of these more rapidly mutating bacteria and try developing some immunological memory instead of continually having this escalating fight with antibiotics.

That's gonna be a long, hard slog and could easily run into exactly the same problem that antibiotics do; changes to the antigen that render the vaccine useless. I'm not saying it's impossible but there need to be other approaches taken as well, like not over-using antibiotics in general.

That is very true, but some of the factors that lead to antibiotic resistance, namely incomplete/inconsistent use of the chemical agent, isn't going to be a factor. At least not in my mind, but my highest level of immunology education was in dental school and I sit around cutting teeth and prescribing amoxicillin all day, so what do I know. I'm at least a minor part of the problem.

That's not clear at all. Vaccines *still* work in a dynamic system ('life finds a way ...') and there will be selective pressures for the little critters to escape whatever bullet you send them.

And we're finding that this 'incomplete / inconsistent' use theory is really a small issue. We have impressively little good info on how long to use a given antibiotic.

But the long, hard slog is correct. This is a war - and so far, the bugs are winning. They outnumber you a couple of billion to one even in your own body. Think of that - you're outnumbered even in yourself....

That depends on if you count yourself as one person or as a couple of billion immune cells.

We discussed colistin in Pharmacology in the late 70's and due to its renal toxicity I never used it or saw it used up and until retirement last year. I note that my work became almost all outpatient and some less likely to run in to these bugs. But my practice was heavily based on causing immunosuppression. The re-emergence of this drug due to need while juggling what we felt was unacceptable toxicity and now its failure is quite sobering.

There are several other drugs that I used to lump into the colistin renally toxic group that many of you have already used: neomycin (Neosporin)and bacitracin(triple antibiotic) for example topically (on the skin only). They are quite distinct chemically, however.

Adverse reactions aren't the problem. Bacteriophages attack prokaryotes not eukaryotes. Historically the problem with phage therapy has been the need to wait for successive generations of phages to evolve in response to an in vitro culture of the resident infection and produce lethal results. In other words, it's just too fucking time-consuming. Aggressive bacterial infections move with astonishing speed. The Soviets had some limited success, but the speed and efficacy of antibiotics just couldn't be touched by phages.

That all changes when you can rapidly sequence the infection colony genome then employ direct editing of a stock phage and produce large quantities in perhaps a day; all this is very much a possibility with tech we have already. The only stumbling block is cutting costs. I have a friend that's done a fair amount of work in a research lab using these tools and the takeaway is that it just keeps getting cheaper by the day.

Adverse reactions ARE a potential issue. I know that bacteriophage aren't attacking eukaryotic cells, but they are a foreign substance in the body and that most definitely has the chance to trigger a reaction. It's a well-known problem for biotherapeutics.

There are plenty of phages that don't produce significant reactions in the human immune system and provided your changes for bacteriophage behavior don't trigger an antigen response then there isn't much of a problem. As for attacking the wrong bacteria, that's a bit of a red herring given that the application for this would nominally be resistant cases where whether it nukes your intestinal biome is of secondary concern to the fact that you are going to fucking die.

Y'all are so busy finding reasons it won't work when the reality is that these toolsets are already in development in different contexts.

It's extremely depressing how often these types of articles are making the rounds nowadays. It's getting to be every couple weeks it seems like there's a new report of how we're dooming ourselves to one day be wiped out by super bacteria.

Kind of a side point to the discussion, but these aren't actually super anything.